Polyomavirus large- and small-T relieve middle-T-induced cell cycle arrest in normal fibroblasts

Alain Marti1, Kurt Ballmer-Hofer1

  • 1Institute of Medical Radiobiology at the Paul Scherrer Institute and of the University of Zürich, 5232- Villigen-PSI, Switzerland1.

Insights

Mouse polyomavirus T antigens regulate cell cycle entry. Small-T antigen (ST) cooperates with middle-T (MT) and large-T (LT) to stimulate growth-arrested cells, revealing ST

Area of Science:

  • Cellular biology
  • Virology
  • Molecular oncology

Background:

  • Papovavirus tumor antigens are crucial tools for studying cell growth regulation.
  • Understanding how viral proteins influence the cell cycle is key to cancer research.

Purpose of the Study:

  • To investigate the roles of mouse polyomavirus small-, middle-, and large-T antigens in stimulating cell cycle entry.
  • To elucidate the cooperative interactions among these T antigens in regulating cell proliferation.

Main Methods:

  • Microinjection of REF52 fibroblasts with cDNAs encoding mouse polyomavirus T antigens.
  • Analysis of cell cycle progression (S phase entry) in response to T antigen expression and serum stimulation.

Main Results:

  • Middle-T antigen expression alone inhibited serum-induced cell cycle stimulation.
  • Coexpression of small-T antigen with middle-T antigen released arrested cells into S phase.
  • Simultaneous expression of middle-T and large-T antigens induced cell cycle entry even without serum.

Conclusions:

  • Cooperation among polyomavirus T antigens is essential for T antigen-mediated cell cycle stimulation in growth-arrested cells.
  • Small-T antigen plays a novel role in signaling to mitogenic pathways, cooperating with other T antigens.

Related Concept Videos

Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...